Interim phase 1 results for SQ3370 in advanced solid tumors.
Authors: Sant P. Chawla, Kathleen Batty, Masa Aleckovic, Vivek Bhadri, Nam Bui, Alexander David Guminski, Jose Manuel Mejia Oneto, Sangeetha Srinivasan, James Fredric Strauss, Vivek Subbiah, Mia C. Weiss, Rosalind Wilson, Nathan A. Yee, Michael Zakharian, Vineet Kwatra
Journal: Journal of Clinical Oncology (2022)

3085 Background: SQ3370, a novel therapy, utilizes Shasqi’s proprietary Click Activated Protodrugs Against Cancer (CAPAC) platform where mutually-reactive click chemistry groups release Doxorubicin (Dox) at the tumor site minimizing systemic exposure. In animals, SQ3370 enhanced survival, T-cell infiltration and antitumor responses in injected and non-injected tumors. Minimal to no toxicity, including no cardiotoxicity was seen in up to 9-fold dose increases in animals. Conventional Dox can induce cardiomyopathy at incidences of 1-20% for cumulative doses from 300-500 mg/m 2 in humans and re-treatment with Dox is less effective in heavily pre-treated patients (pts). Here we report interim results of the Phase 1 ( NCT04106492 ). Methods: SQ3370 has 2 components: 1) Intratumoral injection of a protodrug-activating biopolymer (SQL70: 10 mL or 20 mL); 2) 5 consecutive daily IV infusions of an attenuated protodrug of Dox (SQP33). Key eligibility includes locally advanced or metastatic solid tumors, ≤300 mg/m 2 prior exposure to Dox, ECOG 0-1 and no limit to prior systemic therapies. Primary objectives include safety and determining Phase 2 dose. Dose escalation was assessed in 2 stages: 1) accelerated titration; 2) 3+3 design. Results: As of 31JAN2022 data cut, 26 pts were treated, 21 with 10 mL biopolymer (bp) and 5 with 20 mL bp over 9 dose escalation protodrug cohorts. MTD has not been reached. Median age was 61 years (26-84), 62% were females, and 69% were ECOG 1. Prior procedures included surgery (89%) and radiation (62%). At study entry, 77% of pts had metastases with a median number of metastatic sites being 2 (1-5); most frequently lung (50%). Tumors were sarcoma (73%), breast cancer (7.7%), gyne (7.7%) and other (11.5%). Twenty-four of 26 (92%) pts received prior systemic therapies with 50% receiving prior Dox. Median number of prior systemic therapies was 2 (1-7). Of the 26 pts, 62% received &gt; 500 mg/m 2 cumulative Dox given as SQP33. Median duration of treatment was 2 cycles (1-12). Most frequent AEs, regardless of causality, for the 10 mL bp group included nausea (n = 11), fatigue (n = 9) and anemia (n = 6), and for the 20 mL bp group included anemia (n = 3) and nausea (n = 2). Ejection fraction (LVEF) remained normal during the study period. No AEs that led to discontinuation or death were related to SQ3370 by investigator. At a median follow-up of 9.2 wks (3-37), 21 pts were evaluable. SD was best response in 71%. Median duration of SD was 80-dys (37-186) corresponding to an overall disease control rate (CR+ PR+ SD x 30-dys) of 71% (68% in 10 mL bp; 100% in 20 mL bp). The remainder of pts had PD as best response. Over 38% of pts remain on drug. Conclusions: SQ3370 with 10 mL or 20 mL biopolymer was well tolerated in pts with half being re-treated with Dox. Although &gt; 60% of pts received &gt; 500 mg/m 2 cumulative Dox given as SQP33, LVEF remained normal. Preliminary evidence of disease control was observed in pts despite heavy prior pre-treatment and high cancer burden. Dose escalation is ongoing. Clinical trial information: NCT04106492.